The purpose of this funding opportunity announcement (FOA)
is to 1) expand the collection of clinical data and biological specimens in
the NINDS Parkinson’s Disease Biomarkers Program (PDBP), a community research
resource, to include data from patients with Lewy Body Dementias (including
Dementia with Lewy Bodies and Parkinson's Disease with Dementia), and 2) to
support hypothesis-driven clinical research to discover biomarkers that will
improve the efficiency and outcome of Phase II clinical trials for the Lewy
Body dementias and to provide an expansion of this existing research resource
center for dissemination of information and access by the scientific community
for further advancing research in this field. Applications may include both
of these goals if justified.

Key Dates

Posted Date

February 22, 2016

Open Date (Earliest Submission Date)

April 10, 2016

Letter of Intent Due Date(s)

April 10, 2016

Application Due Date(s)

May 10, 2016, by 5:00 PM local time of applicant organization.
All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted in response to this
FOA.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

July 2016

Advisory Council Review

August 2016

Earliest Start Date

September 2016

Expiration Date

May 11, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

In 2012, the National Institute of Neurological Disorders
and Stroke (NINDS) established a Parkinson’s Disease Biomarkers Program (PDBP)
(https://pdbp.ninds.nih.gov/) for the
purpose of rapidly identifying and developing potential biomarkers that would
improve the efficiency and outcome of Phase II clinical trials and ultimately, advance
the development of treatments for Parkinson's Disease (PD). Originally
composed of a consortium of 10 scientific projects, the PDBP currently contains
clinical, neuroimaging, and/or biospecimen data on over 1300 subjects, and is
expanding to include data and specimens from BioFIND, the Udall Centers, the National
Brain and Tissue Resource for PD & Related Disorders, and other NINDS
Parkinson's disease-related projects. While the PDBP has been very successful
in collecting and distributing standardized, high-quality, longitudinal
clinical and biological data on patients with PD, recent workshops have
identified opportunities for increasing the PDBP's utility by broadening the
patient groups it includes.

On May 1-2, 2013, the NINDS collaborated with the National Institute
on Aging (NIA) in organizing "Alzheimer's Disease-Related Dementias:
Research Challenges and Opportunities" (http://www.ninds.nih.gov/funding/areas/neurodegeneration/workshops/adrd2013/index.htm).
This workshop was part of the 2012 National Plan to Address Alzheimer's
Disease, and was complementary to NIA's Alzheimer's Disease Research Summit
2012. One of the Alzheimer's Disease-related dementias (ADRD) that was
discussed at length during this workshop was Lewy Body Dementia (LBD, including
Parkinson's Disease Dementia and Dementia with Lewy Bodies). Scientists who
were expert in the LBDs developed prioritized research recommendations for
advancing our understanding of this neurodegeneration. One of the top
recommendations called for the creation of longitudinal clinical, biological,
and imaging resources for the LBDs. Additional recommendations called for
identifying genetic/epigenetic markers, developing diagnostic imaging
approaches, and developing biomarkers for LBD. It was recognized that all of
the latter recommendations could be facilitated by the establishment of the
longitudinal resources endorsed by the former recommendation.

Shortly after this, on January 6-7, 2014, NINDS organized
the “Parkinson’s Disease 2014: Advancing Research, Improving Lives” conference
to inform ongoing and future efforts in PD research (http://www.ninds.nih.gov/research/parkinsonsweb/PD2014/index.htm).
This conference provided an opportunity for neuroscience researchers,
physicians, public and private stakeholders, and members of the public to
discuss the significant challenges and identify the highest priorities for
advancing basic, translational and clinical research on PD. Working groups
from each of these three topic areas developed prioritized research
recommendations designed to address emerging opportunities and critical needs
for PD. Non-motor symptoms, particularly cognitive impairment in PD, were
ranked among the top priorities, as a key target for clinical trials by the
Clinical Research working group and as an important focus for defining disease
signatures by the Translational Research working group.

Scientific
Areas of Research Interest

Both of these workshops highlighted the scientific and
stakeholder communities' keen interest in having an improved understanding of
the pathophysiology, risks for, and early diagnosis of conditions in which
parkinsonism and cognitive impairment co-occur. Since current research
suggests that different pathophysiological mechanisms may underlie the numerous
syndromes in which Parkinson's disease and dementia are co-morbid, this FOA
invites applications to expand the NINDS PDBP's current collection of
longitudinal clinical and biospecimen data to include data and samples from
subjects who have been diagnosed with the LBDs, i.e., Parkinson's Disease with
Dementia (PDD) or Dementia with Lewy Bodies (DLB).

2) Hypothesis-driven clinical research to discover potential
biomarkers for the LBDs. Proposed biomarkers may be based on a single measure
or a panel of measurements, and may seek to improve differential diagnosis,
identify risk of disease, or predict disease progression. It is preferable for
applicants to have access to subjects with either PDD or DLB (or to both
populations) and be collecting clinical data and biological specimens from
them. However, high-quality data and samples available from other sources may
be used as a sole resource or in addition to new data collection. All
applicants are encouraged to use existing data and specimens in the PDBP for
control data, though additional controls may be proposed if appropriate and
unavailable in the PDBP. In cases where other studies or repositories are
being used, permission should be obtained from the source prior to application
submission See also the instructions in Section IV.2.

Ideally, studies should be longitudinal. Whereas whole
blood for DNA and PBMCs need only be submitted once (at the time of initial
visit), longitudinal samples (other than CSF) and associated clinical data
should be collected every six months. CSF should be collected at least once per
year for the duration of the grant. Biospecimen and clinical data collection
for a given time point must co-occur at the same subject visit and be submitted
to the NINDS Biomarker Repository and the PDBP Data Management Resource (DMR)
within 24 hours of each visit. Cross-sectional studies in unique
populations may be acceptable, but applicants are encouraged to contact program
staff to discuss this option. For all studies, a timeline for data and
biospecimen collection must be included and justified in the application.

Ancillary studies to existing cohorts for the collection of
new data and biospecimens may be appropriate. However, subjects enrolled
in biomarker studies as a component of existing, ongoing clinical trials are
not appropriate for this FOA because of the risk of un-blinding and the unknown
impact of the tested therapeutics on pathophysiology. All applicants are
encouraged to focus on the recruitment and inclusion of women and minorities,
as well as individuals from other populations that are traditionally
underrepresented in clinical research. Although not required, applications
with special outreach programs to such populations will be considered to be a
high priority for this FOA. For further details, see: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-089.html.

Note that costs for biospecimen collection are not included
as a component of the NINDS Biomarker Repository, and some costs for the
biospecimen banking will be borne by the grantees utilizing this resource. In the
case of PBMCs, the NINDS Cell Repository will generate the cell lines and cover
the costs of the kit components required for collection. When planning the
application budget, applicants are strongly advised to consult with the NINDS
Biomarker Repository staff (https://www.biosend.org/).

All applications will be required to collect standard PDBP
clinical instruments (see: https://pdbp.ninds.nih.gov/jsp/data-management-resource.jsp)
in addition to the Neuropsychiatric Inventory. If additional clinical
assessments are proposed, the NINDS strongly encourages researchers to use
those endorsed by the NINDS Common Data Elements for PD (see: http://www.commondataelements.ninds.nih.gov/PD.aspx#tab=Data_Standards).
Biological specimens should conform to the specimen collection protocols of the
NINDS Biospecimen Repository (see: https://www.biosend.org/). Consent forms must make it
clear that any biological samples and de-identified clinical data will be
shared with academics or industry and must be consistent with the NINDS Biomarker
Repository and NINDS PDBP DMR requirements and achieving the goals of the
program.

If an application plans to utilize the infrastructure or
resources of existing projects, it must not interfere with the parent study
and must not place undue burden on participants. Approved procedures and
policies from the parent study must be followed. Assurance that all samples
and data will be collected under proper consent to allow broad sharing should
be documented. Prior to award, the applicant must provide to NINDS a
memorandum of understanding signed by the applicant, an appropriate
representative of the applicant institution, the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) of the parent clinical study and his or her
academic institution, an appropriate representative of the sponsor of the
parent clinical study, if applicable and not one of the above. This memorandum
will confirm agreement among the various parties and will outline the terms and
conditions of the agreement in the following areas all of which must be
compliant with PDBP policy requirements: 1) ownership, analysis, access and
release of data from the ancillary studies; 2) method and timing of access to
the data from the parent clinical study that are needed to analyze the
ancillary studies; 3) documentation of quality assurance procedures for both
the parent clinical study and the ancillary studies; 4) documentation of Data
and Safety Monitoring procedures for the parent clinical study and ancillary
study if appropriate; 5) ownership of intellectual property developed by the
ancillary studies; and 6) plan for publication of the ancillary study results,
as appropriate and consistent with achieving the goals of the program.

Animal or other disease model studies are not appropriate
for this FOA. Clinical trials are not appropriate for this FOA. Replication
studies or validation studies of commonly-used approaches are strongly
discouraged. Projects that propose the collection of biological specimens and
data that will not be submitted to the NINDS Biomarker Repository/DMR
respectively will not be review.

Applications proposing efforts that are duplicative of DMR
functions or responsibilities will not be funded. Activities that are the
sole purview of the DMR include: 1) development of standardized electronic data
forms, data formats and software for use across multiple cohorts and projects;
2) development of software to support subject scheduling, site tracking, and
facilitation and coordination of de-identified clinical and biospecimen data
collection across multiple new and existing cohorts and projects through an
easy to use web-based entry system for submitters; 3) quality assurance
checks of data entry and collection; 4) development of a user-friendly query
system for users to evaluate availability of data and biospecimens within and
across PD biomarker projects; 5) development of aggregate data report formats
that are user-friendly and supported by well documented data
dictionaries; 6) training for both data submitters and data users; 7)
coordination of data and biospecimen summary reports and postings in
collaboration with the NINDS Biomarker Repository; and 8) public outreach for
data submission and data use. Development of all electronic data entry
forms and quality assurance checks of de-identified data will be done by the
DMR. For those with existing studies already utilizing a data management core
or resource, data must be federated with the DMR as appropriate and consistent
with achieving the goals of the program. Deposition of all data into the PDBP
DMR should occur in real time.

Milestones
and Timeline

Milestones for all projects will specify compliance with
NINDS Biomarker Repository and DMR terms. Annual milestones must be
provided in the context of a study timeline. These milestones will
provide clear indicators of a project's continued success or emergent
difficulties. Milestones are goals that create go/no-go decision points in the
project and must include clear and quantitative criteria for success.
Milestones should include timely subject recruitment, complete, clean and
accurate data submission, and quality accepted collection and submission of
biospecimen samples. Achievement of milestones will be evaluated by
NINDS, and funding of non-competing award years will depend on milestone
accomplishment. Both data and biospecimen collection must meet DMR and
NINDS Biomarker Repository standards. Note that these awards will be
managed as cooperative agreements; therefore, projects that do not comply with terms,
conditions, and established milestones of the award and of this program may be
terminated early.

Due to the unique requirements of the NINDS PDBP, applicants
are strongly encouraged to consult with NINDS Scientific/Research Staff early
on when planning an application (see Agency contacts, Section VIII). This
early contact will provide an opportunity to clarify the applicant's
understanding of the goals of this FOA and NINDS’ policies and guidelines,
including those pertaining to the PDBP DMR and NINDS Biomarker
Repository. These discussions also provide important information and
guidance on how to develop an appropriate timeline and milestone plan, which
are subject to peer review under this program.

Cooperative Agreement: A support mechanism used when there
will be substantial Federal scientific or programmatic involvement.
Substantial involvement means that, after award, NIH scientific or program
staff will assist, guide, coordinate, or participate in project activities. See
Section VI.2 for additional information about the substantial involvement for
this FOA.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

NINDS intends to commit $3,500,000 in FY 2016 to fund
5-7 awards.

Award Budget

Application budgets are not limited but need to reflect the
actual needs of the proposed project.

Award Project Period

The maximum project period is 5 years.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to
apply.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.

Required
Registrations

Applicant
Organizations

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping
applications under review at the same time. This means that the NIH will
not accept:

A new (A0) application that is submitted before issuance of the
summary statement from the review of an overlapping new (A0) or resubmission
(A1) application.

A resubmission (A1) application that is submitted before issuance
of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application
pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must obtain the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, including Supplemental
Grant Application Instructions except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed. The application must identify key personnel in the
application whose responsibility will be to ensure and facilitate data quality,
transfer, sharing, and biological specimen submission to the DMR and NINDS
Biomarker Repository.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed. As noted above, costs for biospecimen collection are not
included as a component of the NINDS Biomarker Repository; some costs for
biospecimen banking should be included in the applicant's budget.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Research
Strategy: Applications should provide details on how the application
will comply with PDBP DMR and NINDS Biospecimen Repository policies and
procedures. If additional measurements are proposed, the applicant should
indicate whether these comply with NINDS common data elements. .

Milestones are goals that create go/no-go decision points in
the project; all applicants must include milestones that specify clear and
quantitative criteria for success. At minimum, milestones should include
timelines for 1) subject recruitment, 2) complete, clean and accurate data
submission, and 3) quality accepted collection and submission of biospecimen samples.
All proposed milestones should conform to the policies and procedures of the
PDBP DMR and NINDS Biomarker Repository.

Letters
of Support: If an application plans to utilize the
infrastructure or resources of existing projects letters of support from the
project leadership detailing approval, feasibility, terms of collaboration and
data sharing must be included. In cases where other studies or repositories are
being used, permission should be obtained from the source prior to application
submission and documented in the application.

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans as provided in the SF424 (R&R)
Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Appendix:
Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions
for completing Planned Enrollment Reports as described in the SF424 (R&R)
Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions
for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH
Grants Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier
and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the
requirement for obtaining a unique entity identifier and for completing and
maintaining active registrations in System for Award Management (SAM), NATO
Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and
Grants.gov

4. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to
submit applications before the due date to ensure they have time to make any
application corrections that might be necessary for successful submission. When
a submission date falls on a weekend or Federal
holiday, the application deadline is automatically extended to the next
business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date and time. If a Changed/Corrected application is submitted after the
deadline, the application will be considered late. Applications that miss the
due date and time are subjected to the NIH Policy on Late Application
Submission.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically. If you encounter a system issue beyond your control that
threatens your ability to complete the submission process on-time, you must
follow the Guidelines
for Applicants Experiencing System Issues. For assistance with application
submission, contact the Application Submission Contacts in Section VII.

Important
reminders:

All PD(s)/PI(s) must include their eRA Commons ID in
the Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS
number it provides on the application is the same number used in the
organization’s profile in the eRA Commons and for the System for Award Management.
Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness and compliance with application instructions by the Center for
Scientific Review and responsiveness by components
of participating organizations, NIH. Applications that are incomplete, non-compliant
and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an
important problem or a critical barrier to progress in the field? Is there a
strong scientific premise for the project? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field? Is the collection proposed important to
the development of this NINDS resource and will it be useful to future
researchers for biomarker discovery? Is the project within the scope and does
it further the goals of biomarker discovery?

Investigator(s)

Are the PD(s)/PI(s), collaborators,
and other researchers well suited to the project? If Early Stage Investigators
or New Investigators, or in the early stages of independent careers, do they
have appropriate experience and training? If established, have they
demonstrated an ongoing record of accomplishments that have advanced their
field(s)? If the project is collaborative or multi-PD/PI, do the investigators
have complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and
seek to shift current research or clinical practice paradigms by utilizing novel
theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies, instrumentation,
or interventions novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy,
methodology, and analyses well-reasoned and appropriate to accomplish the
specific aims of the project? Have the investigators presented strategies to
ensure a robust and unbiased approach, as appropriate for the work proposed? Are
potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed? Have
the investigators presented adequate plans to address relevant biological
variables, such as sex, for studies in vertebrate animals or human subjects?
Are milestones addressing timely subject recruitment, complete, clean and
accurate data submission, and quality collection and submission of biospecimen
samples included with the application? Do they create go/no-go decision points
in the project and include clear and quantitative criteria for success?
Is the approach compliant with PDBP policies and procedures?

If the project involves human
subjects and/or NIH-defined clinical research, are the plans to address 1) the
protection of human subjects from research risks, and 2) inclusion (or
exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as
well as the inclusion or exclusion of children, justified in terms of the
scientific goals and research strategy proposed?

Environment

Will the scientific environment in
which the work will be done contribute to the probability of success? Are the
institutional support, equipment and other physical resources available to the
investigators adequate for the project proposed? Will the project benefit from
unique features of the scientific environment, subject populations, or
collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human
subjects but does not involve one of the six categories of research that are
exempt under 45 CFR Part 46, the committee will evaluate the justification for
involvement of human subjects and the proposed protections from research risk
relating to their participation according to the following five review
criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3)
potential benefits to the subjects and others, 4) importance of the knowledge
to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human
subjects and meets the criteria for one or more of the six categories of
research that are exempt under 45 CFR Part 46, the committee will evaluate: 1)
the justification for the exemption, 2) human subjects involvement and
characteristics, and 3) sources of materials. For additional information on
review of the Human Subjects section, please refer to the Guidelines for the Review of Human
Subjects.

Inclusion of Women, Minorities,
and Children

When the proposed project involves
human subjects and/or NIH-defined clinical research, the committee will
evaluate the proposed plans for the inclusion (or exclusion) of individuals on
the basis of sex/gender, race, and ethnicity, as well as the inclusion (or
exclusion) of children to determine if it is justified in terms of the
scientific goals and research strategy proposed. For additional information on
review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion
in Clinical Research.

Vertebrate Animals

The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following criteria: (1) description of proposed procedures
involving animals, including species, strains, ages, sex, and total number to
be used; (2) justifications for the use of animals versus alternative models
and for the appropriateness of the species proposed; (3) interventions to
minimize discomfort, distress, pain and injury; and (4) justification for
euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia
of Animals. Reviewers will assess the use of chimpanzees as they would any
other application proposing the use of vertebrate animals. For additional
information on review of the Vertebrate Animals section, please refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the
project presents special opportunities for furthering research programs through
the use of unusual talent, resources, populations, or environmental conditions
that exist in other countries and either are not readily available in the
United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the
information provided in this section of the application, including 1) the
Select Agent(s) to be used in the proposed research, 2) the registration status
of all entities where Select Agent(s) will be used, 3) the procedures that will
be used to monitor possession use and transfer of Select Agent(s), and 4) plans
for appropriate biosafety, biocontainment, and security of the Select Agent(s).

For projects involving key biological and/or chemical resources,
reviewers will comment on the brief plans proposed for identifying and ensuring
the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the
budget and the requested period of support are fully justified and reasonable
in relation to the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the NINDS, in
accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in
response to this FOA.

Applications will be assigned to the appropriate NIH
Institute or Center. Applications will compete for available funds with all
other recommended applications submitted in response to this FOA. Following
initial peer review, recommended applications will receive a second level of
review by the National Advisory Neurological Disorders and Stroke (NANDS)
Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities. Such
priorities include compliance with the policies and procedures of the PDBP and
NINDS Biospecimen Repository.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons. Refer to Part 1 for dates for peer review, advisory council
review, and earliest start date.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA)
will be provided to the applicant organization for successful applications. The
NoA signed by the grants management officer is the authorizing document and
will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described
in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be
subject to terms and conditions found on the Award
Conditions and Information for NIH Grants website. This includes any
recent legislation and policy applicable to awards that is highlighted on this
website.

Recipients of federal financial
assistance (FFA) from HHS must administer their programs in compliance with
federal civil rights law. This means that recipients of HHS funds must ensure
equal access to their programs without regard to a person’s race, color, national
origin, disability, age and, in some circumstances, sex and religion. This
includes ensuring your programs are accessible to persons with limited English
proficiency. HHS recognizes that research projects are often limited in scope
for many reasons that are nondiscriminatory, such as the principal
investigator’s scientific interest, funding limitations, recruitment
requirements, and other considerations. Thus, criteria in research protocols
that target or exclude certain populations are warranted where
nondiscriminatory justifications establish that such criteria are appropriate
with respect to the health or safety of the subjects, the scientific study
design, or the purpose of the research.

For additional guidance regarding how the provisions apply to
NIH grant programs, please contact the Scientific/Research Contact that is
identified in Section VII under Agency Contacts of this FOA. HHS provides
general guidance to recipients of FFA on meeting their legal obligation to take
reasonable steps to provide meaningful access to their programs by persons with
limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html.
The HHS Office for Civil Rights also provides guidance on complying with civil
rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html;
and http://www.hhs.gov/ocr/civilrights/understanding/index.html.
Recipients of FFA also have specific legal obligations for serving qualified
individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
Please contact the HHS Office for Civil Rights for more information about
obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS
Departmental goal to ensure access to quality, culturally competent care,
including long-term services and supports, for vulnerable populations. For
further guidance on providing culturally and linguistically appropriate
services, recipients should review the National Standards for Culturally and
Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable
when State and local Governments are eligible to apply), and other HHS, PHS,
and NIH grant administration policies.

The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.

Adhere to existing PDBP study policies regarding data and
biospecimen sharing and other policies that might be established during the
course of this activity as appropriate;

Report to NINDS Program staff regarding timeline and milestone
achievement during the course of the project, as delineated in the terms and
conditions of award;

Submit annual progress reports during the funding period, in a
format as agreed upon by NINDS program staff;

Accept and implement any other common guidelines and procedures
developed for the PDBP initiative and approved by NINDS program staff;

Coordinate with other projects under the PDBP, including sharing
of data with a centralized data management resource and other PDBP sites as
appropriate;

Attend in-person PDBP meetings up to twice per year organized by
NINDS and present up-to-date findings (including unpublished results) on
ongoing projects.

Awardees are expected to make new information and materials
known to the research community not only at in-person PDBP meetings but also in
a timely manner through publications, web announcements, reports to NINDS
program staff, and other mechanisms.

Publications:

The PD(s)/PI(s) will be responsible for the timely
submission of all abstracts, manuscripts and reviews (co)authored by project
investigators and supported in whole or in part under this Cooperative
Agreement. The PD(s)/PI(s) and Project Leaders are requested to submit
manuscripts to the NIH Project Scientist within two weeks of acceptance for
publication so that an up-to-date summary of program accomplishments can be
maintained. Publications and oral presentations of work conducted under this
Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate
Project Leaders and will require appropriate acknowledgement of NINDS and PDBP
support. Timely publication of major findings is required.

NIH
staff have substantial programmatic involvement that is above and beyond the
normal stewardship role in awards, as described below:

NINDS program staff will have substantial
scientific/programmatic involvement during the conduct of this activity through
technical assistance, advice and coordination. However, the role of NINDS
Project Scientists will be to facilitate and not to direct the
activities.

The NINDS
Project Scientist will:Contribute to the adjustment of research
protocols, project milestones or approaches as warranted;

Serve as a liaison between the awardees, the NINDS Advisory
Council and the larger scientific community;

Coordinate the efforts of the awardee with others engaged in
research on Parkinson's disease and parkinsonisms, including other awardees
under this FOA and those involved in related NINDS programs;

Serve on subcommittees of the PDBP External Liaison Group as
appropriate;

Assist in promoting the availability of data and resources
developed in the course of this project to the scientific community at large;

Assist awardees in the development, if needed, of policies for
dealing with situations that require coordinated action;

Retain the option to recommend the withholding or reduction of
support from any cooperative agreement that either substantially fails to
achieve its goals according to the milestones agreed to at the time of award,
fails to maintain state-of-the-art capabilities, or fails to comply with the
Terms and Conditions of the award (including biospecimen and data sharing as
appropriate).

Areas
of Joint Responsibility include:
None

Other
PDBP Components

Steering
Committee

The NINDS has established an independent steering committee
(SC) to assist in determining the broad direction of the PDBP. The SC
provides input regarding new research findings and the relevance of that in the
context of funded and proposed projects.

Biological
Resource Acquisition Committee

The PDBP Biological Resource Acquisition Committee (BRAC)
evaluates requests for biospecimens based on transparent criteria for
distribution towards PD biomarkers discovery projects. It is intended
that biospecimens be available for research studies by academics and industry
investigators.

Data
Acquisition Committee

The PDBP Data Acquisition Committee (DAC) assures that data
use requests are compliant with data use policy and procedure requirements
prior to data distribution, and monitors any security breaches or other
concerns.

Opportunities
for Partnership

Projects involving partnerships with industry, small
businesses or non-government organizations are encouraged under this FOA.
The policy of the NIH is to make available to the public the results and
accomplishments of the activities that it funds. To ensure that research
resources are made accessible to the broader biomedical community, NIH expects
applicants who respond to this funding opportunity to submit a plan for
appropriately: (1) sharing the research resources generated through any grants
awarded and (2) addressing how they will exercise intellectual property rights,
should any be generated through an award, while making such research resources
available to the broader scientific community consistent with this initiative.
Projects based on existing studies in which databases already exist or have
been created via other resources may maintain those databases under those
projects, but not funded via this program. However, it is expected that
these databases will become federated under the DMR.

Dispute
Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
composed of three members will be convened. It will have three members: a
designee of the Steering Committee chosen without NIH staff voting, one NIH
designee, and a third designee with expertise in the relevant area who is
chosen by the other two; in the case of individual disagreement, the first
member may be chosen by the individual awardee. This special dispute resolution
procedure does not alter the awardee's right to appeal an adverse action that
is otherwise appealable in accordance with PHS regulation 42 CFR Part 50,
Subpart D and DHHS regulation 45 CFR Part 16.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.